Hydrogenation of esters with ru/tetradentate ligands complexes

ABSTRACT

The present invention relates to the field of catalytic hydrogenation and, more particularly, to the use of Ru complexes with tetradentate ligands having at least one amino or imino coordinating group and at least one phosphino coordinating group in hydrogenation processes for the reduction of esters or lactones into the corresponding alcohol or diol respectively.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application is a division of application no. 11/854,906 filed Sep.13, 2007, which is a continuation of International applicationPCT/IB2006/051028 filed on Apr. 4, 2006, the entire content of each ofwhich is expressly incorporated herein by reference thereto.

TECHNICAL FIELD

The present invention relates to the field of catalytic hydrogenationand, more particularly, to the use of Ru complexes with tetradentateligands, in hydrogenation processes for the reduction of esters orlactones into the corresponding alcohol or diol respectively.

BACKGROUND

Reduction of an ester functional group to the corresponding alcohol isone of the fundamental reactions in organic chemistry, and is used in alarge number of chemical processes. In general, two main types ofprocesses are known to achieve such a transformation. Such types ofprocesses are the following:

a) hydride processes, in which a silyl or metal hydride salt, such asLiAlH₄, is used;b) hydrogenation processes, in which molecular hydrogen is used.

From a practical point of view, hydrogenation processes are moreattractive as they can be run using small amounts of catalyst (typically10 to 1000 ppm relative to the substrate) and in the presence of smallquantities or even in the absence of solvent. Furthermore, hydrogenationprocesses do not require the use of highly reactive and expensivehydrides, and do not produce important amounts of aqueous waste.

One of the mandatory and characterizing elements of hydrogenationprocesses is the catalyst or the catalytic system which is used toactivate the molecular hydrogen in view of the reduction. Thedevelopment of useful catalysts or catalytic systems for thehydrogenation of an ester functional group represents still an importantneed in chemistry.

Amongst the few catalysts or catalytic systems known to perform suchreductions one may cite the ruthenium/phosphine complexes, obtained bythe reaction of ruthenium oxide or carboxylate precursor with a mono-,di- or tri-phosphine ligand (an example of which is described byElsevier et al. in Chem. Commun., 1998, 1367). In this type of complexthe ruthenium metal is coordinated only by “acac” ligands and phosphineatoms, limiting thus the diversity of the ligand structure andcoordination sphere around the metal center. As a consequence of suchlittle diversity the tuning of the activity and of the performance ofthe hydrogenation process is not easy. Furthermore, the experimentalconditions require very high pressures (at least 70-130 bars) andtemperatures (120-180° C.).

Therefore, there is a need for hydrogenation processes using alternativecatalysts or pre-catalysts, preferably having a greater diversity in theligand structures and coordination spheres around the metal center andallowing the use of softer experimental conditions.

SUMMARY OF THE INVENTION

The present invention now relates about a hydrogenation process for thereduction of esters, or the like, into alcohols in the presence of abase and at least one complex in the form of a ruthenium complex of atetradentate ligand wherein the coordinating groups consist of two aminoor imino group and two phosphino group. The invention relates also aboutnew ligands and complexes useful for carrying the invention process.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

In order to overcome the problems aforementioned, the present inventionrelates to processes for the reduction by hydrogenation, using molecularH₂, of a C₃-C₇₀ substrate containing one or two esters, or lactones,functional groups into the corresponding alcohol, or diol, characterizedin that the process is carried out in the presence of a base and atleast one catalyst or pre-catalyst in the form of a ruthenium complexesof a tetradentate ligand wherein the coordinating groups consist of atleast one amino or imino group and at least one phosphino group.

According to a particular embodiment of the invention, the substrate canbe a compound of formula (I)

wherein R^(a) and R^(b) represent, simultaneously or independently, alinear, branched or cyclic C₁-C₃₀ aromatic, alkyl or alkenyl group,optionally substituted; orR^(a) and R^(b) are bonded together and form a C₄-C₂₀ saturated orunsaturated group, optionally substituted.

The corresponding alcohols (i.e (II-a) and (II-b)), or the correspondingdiol (II′), of the substrate (I), are of formula

wherein R^(a) and R^(b) are defined as in formula (I).

A compound of formula (II) (i.e. II-a or II-b) will be obtained in thecase where R^(a) and R^(b) are not bonded together, while a compound offormula (II′) will be obtained in the case where R^(a) and R^(b) arebonded together.

It is understood that by “a linear, branched or cyclic . . . aromatic,alkyl, or alkenyl group” it is meant that the R^(a) or R^(b) can be inthe form of, e.g., a linear alkyl group or can also be in the form of amixture of the type of groups, e.g. a specific R^(a) may comprises alinear alkyl, a branched alkenyl, a (poly)cyclic alkyl and an arylmoiety, unless a specific limitation to only one type is mentioned.Similarly, in all the below embodiments of the invention when a group ismentioned as being in the form of more than one type of topology (e.g.linear, cyclic or branched) and/or unsaturation (e.g. alkyl, aromatic oralkenyle) it is meant also a group which may comprise moieties havingany one of the topologies or unsaturations, as above explained.

A particular embodiment of the invention's process is shown in Scheme 1:

According to a further embodiment of the invention, the substrate is anester, or lactone, that will provide an alcohol, or a diol, that isuseful in the pharmaceutical, agrochemical or perfumery industry asfinal product or as an intermediate. Particularly preferred substrate isan ester, or lactone, that will provide an alcohol, or diol, which isuseful in the perfumery industry as final product or as an intermediate.

According to another embodiment of the invention, the substrate is aC₅-C₃₀ compound of formula (I), and in particular one may cite thosewherein R^(a) and R^(b) represent simultaneously or independently alinear, branched or cyclic C₁-C₃₀ aromatic or alkyl group optionallysubstituted, or a cyclic C₅-C₃₀ alkenyl group optionally substituted; orR^(a) and R^(b) are bonded together and form a C₄-C₂₀ saturated orunsaturated linear, branched, mono-, di- or tri-cyclic group, optionallysubstituted.

According to a further embodiment of the invention the substrate is aC₅-C₂₀ compound of formula (I), wherein R^(a) and R^(b) representsimultaneously or independently a linear, branched or cyclic C₅-C₁₈aromatic or alkyl group, optionally substituted, or a cyclic C₅-C₁₈alkenyl group, optionally substituted; or R^(a) and R^(b) are bondedtogether and form a C₄-C₂₀ saturated or unsaturated linear, branched,mono-, di- or tri-cyclic group, optionally substituted.

Furthermore, according to a yet further embodiment, when R^(a) and/orR^(b) represent an alkenyl group then the carbon-carbon double bond isnot terminal and is not conjugated.

Possible substituents of R^(a) and R^(b) are one, two or three halogen,OR^(c), NR^(c) ₂ or R^(c) groups, in which R^(c) is a hydrogen atom, ahalogenated C₁-C₂ group or a C₁ to C₁₀ cyclic, linear or branched alkyl,or alkenyl group, preferably a C₁ to C₄ linear or branched alkyl oralkenyl group. As other possible substituents one may also cite a groupCOOR^(c), which can also be reduced to the corresponding alcohol duringthe invention's process, according to the molar amount of H₂ used, aswell known by a person skilled in the art.

Non-limiting examples of substrates are alkyl cinnamates, sorbates orsalycilates, alkyl esters of natural (fatty or not) acids, Sclareolide,spirolactones, allylic ester, di alkyl diesters, (un)substituted benzoicesters, and β-γ unsaturated esters. In particular, the substrate can beselected from the group consisting of sclareolide, C₉-C₁₅ spirolactonesand C₁-C₄ alkyl esters of4-methyl-6-(2,6,6-trimethyl-1-cyclohexen-1-yl)-3-hexenoic acid. One canalso cite the di alkyl esters of 1,4-dicarboxylate-cyclohexane, the diC₁₋₅ alkyl esters of the C₂₋₁₀ alkanediyl-dicarboxylates, C₁₋₅ alkylcyclopropanecarboxylates, mono-, di- or tri-methoxybenzoic esters.

The process of the invention is characterized by the use, as catalyst orpre-catalyst (hereinafter referred to as complexes unless specifiedotherwise), of a ruthenium complex as described above. The complex canbe in the form of an ionic or neutral species.

According to an embodiment of the invention, the ruthenium complex canbe of the general formula

[Ru(L4)Y₂]  (1)

[Ru(L4)(X)_(n)(Y)_(2-n)](Z)_(n)  (2)

wherein L4 represents a tetradentate ligand wherein the coordinatinggroups consist of at least one amino or imino group and at least onephosphino group; andeach Y represents, simultaneously or independently, CO, a hydrogen orhalogen atom, a hydroxyl group, or a C₁-C₆ alkoxy or carboxylic radical,or also a BH₄ or AlH₄ group;X represents a C₃-C₃₀ mono-phosphine or a solvent;Z represents a non-coordinated anion; andn is 0, 1 or 2.

In particular L4 is a tetradentate ligand, such as a C₈-C₄₅ compound,wherein the coordinating groups consist of two amino or imino group andtwo phosphino group, and in particular the amino groups are a primary(i.e. NH₂) or a secondary (i.e. NH) amino groups.

In a particular embodiment of the invention, in formula (1) or (2), eachY represents, simultaneously or independently, a hydrogen or chlorineatom, a hydroxy radical, a C₁ to C₆ alkoxy radical, such as a methoxy,ethoxy or isopropoxy radical, or a C₁ to C₆ acyloxy radical such as aCH₃COO or CH₃CH₂COO radical. More preferably, each Y represents,simultaneously or independently, a hydrogen or chlorine atom, a methoxy,ethoxy or isopropoxy radical, or a CH₃COO or CH₃CH₂COO radical.

In a particular embodiment of the invention, in formula (2), Xrepresents a mono-phosphine of formula PR^(d) ₃, wherein R^(d) is aC₁-C₁₂ group, such as linear, branched or cyclic alkyl, alkoxy oraryloxy group optionally substituted, substituted or unsubstitutedphenyl, diphenyl or naphthyl or di-naphthyl group. More particularlyR^(d) may represent a substituted or unsubstituted phenyl, diphenyl ornaphthyl or di-naphthyl group. Possible substituents are those citedbelow for L4.

X may also be a solvent, the term “solvent” has to be understoodaccording to the usual meaning in the art and includes compounds used asdiluent in the preparation of the complex or during the invention'sprocess, non limiting examples are dimethylsulfoxide, acetonitrile,dimethylformamide, an alcohol (e.g. an C₁-C₄ alcohol), or also THF,acetone, pyridine or a C₃-C₈ ester or the substrate of the invention'sprocess.

In a particular embodiment of the invention, in formula (2), Zrepresents a halogen atom, a hydroxyl group, or a C₁-C₆ alkoxy, phenoxyor carboxylic radical.

The complex of formula (1) represents, in general for practical reasons,a preferred embodiment of the invention.

According to a particular embodiment of the invention, L4 can be acompound of formula

wherein the dotted lines indicate a single or double bond, z is 1 if thenitrogen atom belongs to an amino group (the dotted lines are singlebonds) or is 0 if the nitrogen atom belongs to an imino group (onedotted line is a double bond);R² and R³, when taken separately, represent, simultaneously orindependently, a linear, branched or cyclic C₁ to C₈ alkyl or alkenylgroup optionally substituted, a C₆ to C₁₀ aromatic group optionallysubstituted, or an OR^(T) or NR^(2′)R^(3′) group, R^(2′) and R^(3′)being a C₁ to C₈ alkyl or alkenyl group; or the groups R² and R³ bondedto the same P atom, when taken together, form a saturated or unsaturatedring optionally substituted, having 4 to 10 atoms and including thephosphorus atom to which the R² and R³ groups are bonded;A represents a —(CR⁹ ₂)_(k)— group or a diphenyl, dinaphthyl, C₅-C₁₂metallocediyl, phenylene (—C₆H₄—) or naphthylene (—C₁₀H₆—) groupoptionally substituted; B represents a diphenyl, dinaphthyl, C₅-C₁₂metallocediyl, phenylene or naphthylene group optionally substituted ora group of formula

R⁹, R¹⁰ and R¹¹, taken separately, represent, simultaneously orindependently, a hydrogen atom, a C₁-C₁₀ linear, branched or cyclicalkyl or alkenyl group optionally substituted or a C₆ to C₁₀ aromaticgroup optionally substituted; two adjacent or geminal R⁹, takentogether, may form a C₅₋₁₀ ring including the carbon atom to which theR⁹ groups are bonded; a R¹⁰ group and a R⁹ group, in α-position to thesame N atom, can be bonded together to form a C₄-C₆ saturated orunsaturated ring; two adjacent R¹¹ groups can be bonded together to forma C₅ to C₁₀ aromatic ring optionally substituted or a C₅-C₁₂metallocenediyl group optionally substituted and including the carbonatom to which the R¹¹ or R⁹ groups are bonded; andk are, simultaneously or independently, equal to 0 or 1.

It is understood that, in any of the present embodiments, themetallocenediyl, such as for example a ferrocenediyl, can be in the formof a metallocene-1,1′-diyl or of a metallocene-1,2-diyl.

Similarly when A and/or B are diphenyl or dinaphthyl groups they arepreferably in their 1,1′ form, and when the A and/or B are phenylene ornaphthylene group they are in a ortho or meta form or for thenaphthylene also as naphthalene-1,8-diyl derivative.

According to a particular embodiment of the invention, L4 can be acompound of formula (4-A) or (4-B):

wherein the dotted lines indicate a single or double bond;R² and R³, when taken separately, represent, simultaneously orindependently, a linear, branched or cyclic C₁ to C₈ alkyl or alkenylgroup optionally substituted, a C₆ to C₁₀ aromatic group optionallysubstituted, or an OR^(2′) or NR^(2′)R^(3′) group, R^(2′) and R^(3′)being a C₁ to C₈ alkyl or alkenyl group; or the groups R² and R³, whentaken together, form a saturated or unsaturated ring optionallysubstituted, having 4 or 5 to 10 atoms and including the phosphorus atomto which the R² and R³ groups are bonded;R⁹, R¹⁰ and R¹¹, taken separately, represent, simultaneously orindependently, a hydrogen atom, a C₁-C₈ linear, branched or cyclic alkylor alkenyl group optionally substituted or a C₆ to C₁₀ aromatic groupoptionally substituted; two adjacent or geminal R⁹, taken together, mayform a, preferably C₅ to C₈, ring including the carbon atom to which theR⁹ groups are bonded; a R¹⁰ group and a R⁹ group, in α-position to thesame N atom, can be bonded together to form a C₄-C₆ ring; two adjacentR″ groups can be bonded together to form a C₆ to C₁₀ aromatic ringoptionally substituted or a C₅-C₁₂ metallocenediyl group optionallysubstituted and including the carbon atom to which the R¹¹ groups arebonded; andk are, simultaneously or independently, equal to 0 or 1.

According to an embodiment of the invention, R² and R³ may represent,simultaneously or independently, a linear, branched or cyclic C₁ to C₆alkyl group optionally substituted, a phenyl group optionallysubstituted; the groups R² and R³, taken together, may form a saturatedor unsaturated ring optionally substituted, having 4, 5, 6 or 7 atomsand including the phosphorus atom to which the R² and R³ groups arebonded. Alternatively, R² and R³ may represents a linear, branched orcyclic C₁ to C₆ alkyl group optionally substituted or an phenyl groupoptionally substituted.

Preferably, ligand L4 is a compound of formula

wherein the dotted lines indicate a single or double bond;R² and R³, taken separately, represent simultaneously or independently alinear, branched or cyclic alkyl group containing 1 to 6 carbon atoms ora phenyl group optionally substituted; or the two R² and R³ bonded tothe same P atom, taken together, form a ring having 5 to 7 atoms andincluding the phosphorus atom to which they are bonded;R⁹, R¹⁰ and R¹¹, taken separately, represent, simultaneously orindependently, a hydrogen atom, a C₁-C₄ linear or branched alkyl groupoptionally substituted or a phenyl group optionally substituted; the twoR⁹, taken together, may form a C₄-C₈, or preferably a C₅-C₇, ringincluding the carbon atom to which the R⁹ groups are bonded; twoadjacent R¹¹, taken together, may form a phenyl group optionallysubstituted and including the carbon atom to which the R¹¹ groups arebonded; andk are, simultaneously or independently, equal to 0 or 1.

Possible substituents of the various groups A, B, R², R³, R⁹, R¹⁰ andR¹¹ are one or two halogen, C₁ to C₁₀ alkoxy, polyalkyleneglycols, halo-or perhalo-hydrocarbon, COOR, NR₂, quaternary amine or R groups, whereinR is a C₁ to C₆ alkyl, or a C₅ to C₁₂ cycloalkyl, aralkyl (such asbenzyl, phenethyl etc.) or aromatic group, the latter being alsooptionally substituted by one, two or three halogen, sulfonates groupsor C₁-C₈ alkyl, alkoxy, amino, nitro, sulfonates, halo- orperhalo-hydrocarbon or ester groups. By “halo- or perhalo-hydrocarbon”it is meant groups such as CF₃ or CClH₂ for instance.

Alternatively the substituents can be, and in particular when the groupsare or contain phenyl groups or moieties, one or two halogen, C₁ to C₅alkoxy or polyalkyleneglycols groups, COOR, NR₂ or R groups wherein R isa C₁ to C₄ alkyl, or a C₅₋₆ cycloalkyl, aralkyl or aromatic group, thelatter being also optionally substituted as above defined.

Alternatively, possible substituents of R⁹, R¹⁰ and R¹¹ are one or twohalogen atoms or R⁸, OR⁸ or NR⁸ ₂, R⁸ being a C₁ to C₆ alkyl groups or aC₁ to C₄ alkyl groups.

According to a specific embodiment of the invention the complexes of theformula (1) or (2) wherein Y is defined as above, and in particularrepresents H or Cl, and L4 represent a ligand of the formulae (4-D),(4-E), (4-F) or (4-G) :

wherein the dotted lines represent a single or double bond and Ph is aphenyl radical, R, taken separately, is C₁-C₅ alkyl or, taken together,are a C₃-C₆ group, and k is 1 or 0.

The ligands of one of the formulae

wherein A, B, R², R³, R⁹, R¹⁰, R¹¹ and k have the same meaning as above,as well as those of formula (4-F) or (4-G) are new, with the exceptionof N,N′-1,2-ethanediylidenebis[2-(diphenylphosphino-) benzenemethanamineand of N,N′-2,3-butanediylidenebis[2-(diphenylphosphino-)benzenemethanamine, and are therefore also an object of the presentinvention.

Similarly the invention complexes where the tetradentate ligand is acompound of formula (2′), (4-B′), (4-C′), (4-F) or (4-G) are also new,with the exception ofdichloro[N,N′-1,2-ethanediylidenebis[2-(diphenylphosphino-κP)benzenemethanamine-κM-Ruthenium,and are also an object of the present invention.

The ligands described above can be obtained by applying standard methodswhich are well known in the state of the art and by the person skilledin the art. Therefore, their preparation does not require a specificdescription. For example one may revert to WO 02/40155.

In general, the complexes of formula (1) can be prepared and isolatedprior to their use in the process according to the general methodsdescribed in the literature. A method is described in the Example.

Moreover, the complexes can be prepared in situ, by several methods, inthe hydrogenation medium, without isolation or purification, just beforetheir use.

One of the possible procedures to advantageously prepare in situ acomplex of formula (1) consists in reacting an appropriate Ru complex offormula [Ru(“diene”)(“allyl”)₂], wherein “diene” represents a cyclic orlinear hydrocarbon containing two carbon-carbon double bonds, conjugatedor not, such as for example 1,5-cyclooctadiene (COD) or norbornadiene,and “allyl” represents a linear or branched C₃ to C₈ hydrocarbon radicalcontaining one carbon-carbon double bond such as methylallyl or allyl,with a non coordinating acid such as HBF₄.Et₂O, and then treating theresulting solution with the required amount of a ligands L4, such asdefined previously, to give a solution of a catalyst according toformula (1). Furthermore, the mixture thus obtained can also be treatedwith a base in the presence of a primary or secondary alcohol.Furthermore, the complexes of formula (I) can be prepared by reacting anappropriate Ru complex such as, [RuCl₂(PPh₃)₃], [RuCl₂(cod)] or[RuCl₂(arene)]₂ with the required amount of a ligands L4, such asdefined previously (cod representing a cyclooctadiene and arene beinge.g. a benzene or naphthalene).

It is also understood that the complex of formula (I) can also beobtained in situ from complexes which have a similar formula and whichin presence of, for example an alcohol and a base, are converted into acompound of formula (I). For example, from a complex wherein X, Y, and Zhave other meaning

To carry out the processes of the invention it is required also to use abase. The base can be the substrate itself, if the latter is basic, acorresponding alcoholate or any base having preferentially a pK_(a)above 11. According to a particular embodiment of the invention the basemay have a pK_(a) above 14. It is also understood that preferably thebase does not reduce itself a substrate of formula (I). As non-limitingexamples one may cite the following type of base: alcoholate,hydroxides, alkaline or alkaline-earth carbonates, phosphazenes, amides,basic alox, siliconates (i.e. silicium derivatives having SiO⁻ or SiRO⁻groups), hydrides such as NaBH₄, NaH or KH.

One can cite, as non-limiting examples, alkaline or alkaline-earth metalcarbonates, such as cesium carbonate, an alkaline or alkaline-earthmetal hydroxides, C₁₋₁₀ amidures, C₁₀₋₂₆ phosphazene or an alcoholate offormula (R¹³O)₂M or R¹³OM′, wherein M is an alkaline-earth metal, M′ isan alkaline metal or an ammonium NR¹⁴ ₄ ⁺, R¹³ stands for hydrogen or aC₁ to C₆ linear or branched alkyl radical and R¹⁴ stands for a C₁ to C₁₀linear or branched alkyl radical, such as sodium or potassiumalcoholates. Of course, other suitable bases can be used.

According to an embodiment of the invention, the base is an alkalinealcoholate of formula R¹³OM′.

As previously mentioned the processes of the invention consist in thehydrogenation of a substrate using a ruthenium complex and a base. Atypical process implies the mixture of the substrate with the rutheniumcomplex, a base and optionally a solvent, and then treating such amixture with molecular hydrogen at a chosen pressure and temperature.

The complexes of the invention, an essential parameter of the process,can be added to the reaction medium in a large range of concentrations.As non-limiting examples, one can cite as complex concentration valuesthose ranging from 50 ppm to 50000 ppm, relative to the amount ofsubstrate. Preferably, the complex concentration will be comprisedbetween 100 and 20000 ppm. It goes without saying that the optimumconcentration of complex will depend, as the person skilled in the artknows, on the nature of the latter, on the nature of the substrate andon the pressure of H₂ used during the process, as well as the desiredtime of reaction.

Useful quantities of base, added to the reaction mixture, may becomprised in a relatively large range. One can cite, as non-limitingexamples, ranges between 5 to 50000 molar equivalents, relative to thecomplex (e.g. base/com=5 to 50000), preferably 20 to 2000, and even morepreferably between 50 and 1000 molar equivalents.

The hydrogenation reaction can be carried out in the presence or absenceof a solvent. When a solvent is required or used for practical reasons,then any solvent current in hydrogenation reactions can be used for thepurposes of the invention. Non-limiting examples include aromaticsolvents such as toluene or xylene, hydrocarbon solvents such as hexaneor cyclohexane, ethers such as tetrahydrofuran or MTBE, polar solventssuch as primary or secondary alcohols such as isopropanol or ethanol, ormixtures thereof. The choice of the solvent is a function of the natureof the complex and the person skilled in the art is well able to selectthe solvent most convenient in each case to optimize the hydrogenationreaction.

In the hydrogenation process of the invention, the reaction can becarried out at a H₂ pressure comprised between 10⁵ Pa and 80×10⁵ Pa (1to 80 bars) or even more if desired. Again, a person skilled in the artis well able to adjust the pressure as a function of the catalyst loadand of the dilution of the substrate in the solvent. As examples, onecan cite typical pressures of 1 to 50×10⁵ Pa (1 to 50 bar).

The temperature at which the hydrogenation can be carried out iscomprised between 0° C. and 120° C., more preferably in the range ofbetween 50° C. and 100° C. Of course, a person skilled in the art isalso able to select the preferred temperature as a function of themelting and boiling point of the starting and final products as well asthe desired time of reaction or conversion.

EXAMPLES

The invention will now be described in further detail by way of thefollowing examples, wherein the temperatures are indicated in degreescentigrade and the abbreviations have the usual meaning in the art.

All the procedures described hereafter have been carried out under aninert atmosphere unless stated otherwise. Hydrogenations were carriedout in open glass tubes placed inside a stainless steel autoclave. H₂gas (99.99990%) was used as received. All substrates and solvents weredistilled from appropriate drying agents under Ar. NMR spectra wererecorded on a Bruker AM-400 (¹H at 400.1 MHz, ¹³C at 100.6 MHz, and ³¹Pat 161.9 MHz) spectrometer and normally measured at 300 K, in CDCl₃unless indicated otherwise. Chemical shifts are listed in ppm.

Example 1 Preparation ofN,N′-bis{[2-(diphenylphosphino)phenyl]methylene}-2,2-dimethyl-1,3-propanediamine(L-5)

Under argon, a solution of 2-(diphenylphosphino)benzaldehyde (522.7 mg,1.8 mmol) and 2,2-dimethyl-1,3-propanediamine (93.3 mg, 0.9 mmol) intoluene (15 mL) was stirred at room temperature for 15h. Then thereaction mixture was heated at 80° C. (oil bath) for 2 h 30 min. Next,the solvent was removed in vacuo, and an orange solid was recovered(476.8 mg, 0.74 mmol, 82%).

¹H NMR (CD₂Cl₂, 400 MHz): δ8.78 (d, J=4.6 Hz, 2H), 7.96 (dd, J=7.7, 4.1Hz, 2H), 7.3-7.2 (m, 24H), 6.87 (dd, J=7.7, 4.1 Hz, 2H), 3.19 (s, 4H),0.69 (s, 6H).

¹³C NMR (CD₂CL₂, 100 MHz): δ160 (d, J=20.2 Hz, CH=N), 140.3 (d, J=17.8Hz, Carom), 137.7 (d, J=20.2 Hz, Carom), 137.4 (d, J=10.5 Hz, Carom),134.4 (d, J=20.2 Hz, CHarom), 134.1 (d, J=20.2 Hz, CHarom), 133.7(CHarom), 130.2 (CHarom), 129.1 (CHarom), 128.9 (d, J =7.3 Hz, CHarom),128.4 (d, J =4.8 Hz, CHarom), 70.7 (CH2), 36.9 (C), 24.4 (CH3).

³¹P{¹H} NMR (CD₂CL₂, 100 MHz): δ-12.8.

This ligand is a novel one, as well as the ruthenium complex comprisingit.

Example 2 Catalytic Hydrogenation of various esters using complexes offormula (1)

a) using pre formed complex

A typical catalytic hydrogenation using preformed RuCl₂(L-1) aspre-catalyst is described below with methyl benzoate as substrate:

Under argon, a solution of methyl benzoate (2.721 g, 20 mmol) in THF (2mL) was added with a syringe, followed by more THF (2×1 mL), to a Keimautoclave equipped with a glass liner containing RuCl₂(L-1) (7.9 mg,0.01 mmol, 0.05 mol %), solid NaOMe (107.9 mg, 2.0 mmol, 10 mol %) andTHF (10 mL). The autoclave was pressurised with hydrogen gas at 50 barsand placed in a thermosttated oil bath set at 100° C. After 2 h 30 min,the autoclave was removed from the oil bath, and cooled in a cold-waterbath. Then, the reaction mixture was diluted with aq. 1N HCl (50 mL) andextracted with MTBE (100 mL). Gas chromatography after silylation of analiquot showed the following products: methyl benzoate (1.7%), benzylalcohol (94.6%), benzoic acid (3.7%). Then, the organic phase was washedsuccessively with aq. 1N KOH (50 mL) and aq. sat. NaCl (3×50 mL), anddried over MgSO₄ anh. Filtration and removal of the solvent in vacuogave a yellow liquid (2.085 g). Purification by flash chromatography onsilica gel with pentane/Et₂O (2/1) as elution mixture gave pure benzylalcohol (1.742 g, 16.1 mmol, 80%) as a colourless liquid.

¹H NMR (CDCl₃, 400 MHz): δ7.38-7.25 (m, 5H), 4.65 (s, 2H), 2.02 (s, 1H).

¹³C NMR (CDCL₃, 100 MHz): δ140.9 (s), 128.6 (d), 127.6 (d), 126.9 (d),62.3 (t).

b) using in-situ formed complex

A typical catalytic hydrogenation using in-situ formed RuCl₂(L-4) aspre-catalyst is described below with methyl benzoate as substrate:

Under argon, a solution of methyl benzoate (2.723 g, 20 mmol) in THF (2mL) was added with a syringe, followed by more THF (2×1 mL), to a Keimautoclave equipped with a glass liner containing [RuCl₂(para-cymene)]₂(6.5 mg, 0.01 mmol, 0.05 mol %), ligand L-4 (12.2 mg, 0.02 mmol, 0.1 mol%), solid NaOMe (108.1 mg, 2.0 mmol, 10 mol %) and THF (10 mL). Then asolution of tridecane (368.8 mg, 0.02 mmol), as internal standard, isadded in THF (2 mL), followed by more THF (2×1 mL). The autoclave wasthen pressurised with hydrogen gas at 50 bars and placed in athermostatted oil bath set at 100° C. After 2 h 30 min, the autoclavewas removed from the oil bath, and cooled in a cold-water bath. Then,the reaction mixture was diluted with MTBE (100 mL) and washedsuccessively with aq. 1N HCl (50 mL) and aq. sat. NaCl (3×50 mL). Gaschromatography after silylation of an aliquot showed the followingproducts: benzyl alcohol (97.4%), benzoic acid (2.6%). GC yield based onthe internal standard gave a yield of 90% of benzyl alcohol.

Using methyl benzoate as a test substrate several complexes (Table 1),bases and solvent, as reported in Table 2, were tested under theseconditions.

TABLE 1 Structure of ligands Structure Name

L-1

L-2

L-4

L-5

L-6 Ligands L-1 to L-4 were prepared according to Rautenstrauch, V. etal in WO 02/40155. Ligand L-6 was prepared according to DuBois, T. D.Inorganic Chem. 1972, 11(4), 718-722.

TABLE 2 Hydrogenation of methyl benzoate using complexes of formula (1)GC yield Test Complex Com/Base¹⁾ Base Solvent (%)²⁾ 1 RuCl₂(L-1)1000/1000000 NaOMe THF 86³⁾ 2 RuCl₂(L-1) 1000/100000  NaOMe THF 95³⁾ 3RuCl₂(L-1) 500/100000 NaOMe THF 95 (81) 4 RuCl₂(L-1) 500/100000 NaOMeTHF⁴⁾ 77 5 RuCl₂(L-1) 500/100000 NaOMe THF⁵⁾ 34 6 RuCl₂(L-1) 500/100000NaOMe Toluene 92 7 RuCl₂(L-1) 500/100000 NaOMe iPrOH 73 8 RuCl₂(L-1)500/100000 NaO^(i)Pr THF 93 9 RuCl₂(L-2) 500/100000 NaOMe THF 99 10RuCl₂(L-4) 1000/100000  NaOMe THF⁶⁾ 97 11 RuCl₂(L-5) 1000/100000  NaOMeTHF⁷⁾ 96 12 RuCl₂(L-6) 1000/100000  NaOMe THF⁸⁾ 99 Reaction conditions:Substrate (20 mmol), H₂ gas (50 bars), THF (14 mL) at 100° C. during 2 h30 min. ¹⁾Com/Base: complex/base molar ratio in ppm relative to thesubstrate. ²⁾Based on internal standard (analysed by GC) otherwiseindicated. In brackets isolated yield after chromatography on silicagel. ³⁾Conversion (in %, analysed by GC) of methyl benzoate into benzylalcohol after 1 hour. ⁴⁾Reaction run at 60° C. during 6 h. ⁵⁾Reactionrun with H₂ gas (10 bars) during 6 h. ⁶⁾Complex generated in-situ withL-4 and [RuCl₂(para-cymene)]₂ ⁷⁾Complex generated in-situ with L-5 and[RuCl₂(para-cymene)]₂ ⁸⁾Complex generated in-situ with L-6 and[RuCl₂(para-cymene)]₂ and reaction run during 1 hour.

Several other esters, whose structure and names are described in Table3, were hydrogenated under the conditions described above usingpreformed RuCl₂(L-1). Isolated yield are given in Table 4.

TABLE 3 Structure and names of substrates used Substrate Structure Name1

Methyl benzoate 2

iso-Propyl benzoate 3

Methyl 4-(methoxy) benzoate 4

Methyl 4-(trifluoromethyl) benzoate 5

Methyl phenylacetate 6

Methyl 3-(phenyl) propanoate 7

Methyl octanoate 8

Dimethyl glutarate 9

5-Pentyl-dihydro-furan-2-one 10

6-Pentyl-tetrahydro-pyran-2-one

TABLE 4 Hydrogenation of esters using RuCl₂(L-1) Isolated Conv. yieldTest Sub. (%) (%) 1 1 95 81 2 2 97 91 3 3 94 82 4 4 85 61 5 5 96 83 6 697 89 7 7 97 88 8 8 99 93 9 9 94 91 10 10 94 86 Sub.: Substrate asdescribed in Table 3. Conv.: Conversion (in %, analysed by GC aftersilylation) of ester to alcohol after 2 h 30 min. Reaction conditions:Substrate (20 mmol), H₂ gas (50 bars), RuCl₂(L-1) 0.05 mol %, NaOMe 10mol %, THF (14 mL) at 100° C. during 2 h 30 min.

Example 3 Chemoselective Hydrogenation of Esters Using with Complexes ofFormula (1)

Hydrogenation of methyl 3-cyclohexene-1-carboxylate was taken as modelsubstrate using complexes RuCl₂(L-1) and RuCl₂(L-2). Structures ofligands are described in Table 1 and the results are summarised in Table5.

Typical reaction condition is described bellow for RuCl₂(L-1):

Under argon, a solution of methyl 3-cyclohexene-1-carboxylate (2.810 g,20 mmol) in THF (2 mL) was added with a syringe, followed by more THF(2×1 mL), to a Keim autoclave equipped with a glass liner containingRuCl₂(L-1) (8.4 mg, 0.01 mmol, 0.05 mol %), solid NaOMe (109.7 mg, 2.0mmol, 10 mol %), and THF (10 mL). Then, the autoclave was pressurisedwith hydrogen gas at 50 bars and placed in a thermosttated oil bath setat 100° C.

After 2 h 30 min, the autoclave was removed from the oil bath, andcooled in a cold-water bath. The glass liner was removed from theautoclave, and the reaction mixture was diluted with citric acid 10% w/w(25 mL) and extracted with MTBE (100 mL). Gas chromatography aftersilylation showed the following products: methyl3-cyclohexene-l-carboxylate (2%), cyclohexanemethanol (2%), 3-cyclohexene-1-methanol (91%), 3-cyclohexen-1-carboxylic acid (2%),3-cyclohexene-1-methyl 3-cyclohexene-l-carboxylate (3%). Purification byflash chromatography on silica gel with pentane/Et₂O (10/1→1/1) aselution mixture gave the desired 3-cyclohexene-1-methanol (1.768 g, 15.4mmol, 77%) as a colorless liquid.

¹H NMR (CDCl₃, 400 MHz): δ5.68 (s, AB syst., 2H), 3.57-3.49 (m, AB syst,2H), 2.2-2 (m, 3H), 1.9-1.7 (m, 4H), 1.35-1.2 (m, 1H).

¹³C NMR (CDCL₃, 100 MHz): 6 127.1 (CH), 125.9 (CH), 67.8 (CH2), 36.32(CH), 28.1 (CH2), 25.2 (CH2), 24.6 (CH2).

TABLE 5 Chemoselectivity observed with complexes of formula (1)Selectivity Isolated Conv. ROH unsat./ yield Test RuCl₂(L-n) (%) ROHsat. (%) 1 L-1 91 98/2 77 2 L-1   84¹⁾ 98/2 67 3 L-2 82 97/3 66 Conv.:Conversion (in %, analysed by GC after silylation) of ester to alcoholafter 2 h 30 min. Reaction conditions: Substrate (20 mmol), H₂ gas (50bars), RuCl₂(L-n) 0.05 mol %, NaOMe 10 mol %, THF (14 mL) at 100° C.during 2 h 30 min. ¹⁾Reaction run at 80° C. during 5 h.

1. A process for the reduction by hydrogenation, using molecular H₂, ofa C₃-C₇₀ substrate containing one or two ester or lactone functionalgroups into its corresponding alcohol or diol, which comprises carryingout the process in the presence of a base and at least one catalyst orpre-catalyst in the form of a ruthenium complexes of formula[Ru(L4)Y₂]  (1)[Ru(L4)(X)_(n)(Y)_(2-n)](Z)_(n)  (2 wherein L4 represents a tetradentateligand wherein the coordinating groups consist of at least one amino orimino group and at least one phosphino group; and each Y represents,simultaneously or independently, CO, a hydrogen or halogen atom, ahydroxyl group, or a C₁-C₆ alkoxy or carboxylic radical, or a BH₄ orALH₄ group; X represents a C₃-C₃₀ mono-phosphine or a solvent; Zrepresents a non-coordinated anion; and n is 0, 1 or
 2. 2. The processaccording to claim 1, wherein the coordinating groups consist of twoamino or imino group and two phosphino group, and the amino groups are aprimary or a secondary amino group.
 3. The process according to claim 1,wherein the ruthenium complex is of formula[Ru(L4)Y₂]  (1) wherein L4 and Y have the meaning indicated in claim 1.4. The process according to claim 1, wherein L4 is a ligand of formula

wherein the dotted lines indicate a single or double bond, z is 1 if thenitrogen atom belong to an amino group (the dotted lines are singlebonds) or is 0 if the nitrogen atom belong to an imino group (one dottedlines is a double bond); R² and R³, when taken separately, represent,simultaneously or independently, a linear, branched or cyclic C₁ to C₈alkyl or alkenyl group optionally substituted, a C₆ to C₁₀ aromaticgroup optionally substituted, or an OR^(2′) or NR^(2′)R^(3′) group,R^(2′) and R^(3′) being a C₁ to C₈ alkyl or alkenyl group; or the groupsR² and R³ bonded to the same P atom, when taken together, form asaturated or unsaturated ring optionally substituted, having 4 to 10atoms and including the phosphorus atom to which the R² and R³ groupsare bonded; A represents a —(CR⁹ ₂)_(k)— group or a diphenyl,dinaphthyl, C₅-C₁₂ metallocediyl, phenylene (—C6H₄—) or naphthylene(—C₁₀H₆—) group optionally substituted; B represents a diphenyl,dinaphthyl, C₅-C₁₂ metallocediyl, phenylene or naphthylene groupoptionally substituted or a group of formula

R⁹, R¹⁰ and R¹¹, taken separately, represent, simultaneously orindependently, a hydrogen atom, a C₁-C₁₀ linear, branched or cyclicalkyl or alkenyl group optionally substituted or a C₆ to C₁₀ aromaticgroup optionally substituted; two adjacent or geminal R⁹, takentogether, may form a C₅₋₁₀ ring including the carbon atom to which theR⁹ groups are bonded; a R¹⁰ group and a R⁹ group, in α-position to thesame N atom, can be bonded together to form a C₄-C₆ saturated orunsaturated ring; two adjacent R¹¹ groups can be bonded together to forma C₅ to C₁₀ aromatic ring optionally substituted or a C₅-C₁₂metallocenediyl group optionally substituted and including the carbonatom to which the R¹¹ or R⁹ groups are bonded; and k are, simultaneouslyor independently, equal to 0 or 1; and wherein the substituents of A, B,R², R³, R⁹, R¹⁰ and R¹¹ are one or two halogen, C₁ to C₁₀ alkoxy,polyalkyleneglycols, halo- or perhalo-hydrocarbon, COOR, NR₂, quaternaryamine or R groups, wherein R is a C₁ to C₆ alkyl, or a C₅ to C₁₂cycloalkyl, aralkyl or aromatic group, the latter being also optionallysubstituted by one, two or three halogen, sulfonates groups or C₁-C₈alkyl, alkoxy, amino, nitro, sulfonates, halo- or perhalo-hydrocarbon orester groups.
 5. The process according to claim 1, wherein L4 is aligand of formula (4-B)

wherein the dotted lines indicate a single or double bond; R² and R³,when taken separately, represent, simultaneously or independently, alinear, branched or cyclic C₁ to C₈ alkyl or alkenyl group optionallysubstituted, a C₆ to C₁₀ aromatic group optionally substituted, or anOR^(2′) or NR^(2′)R^(3′) group, R^(2′) and R^(3′) being a C₁ to C₈ alkylor alkenyl group; or the groups R² and R³, when taken together, form asaturated or unsaturated ring optionally substituted, having 4 to 10atoms and including the phosphorus atom to which the R² and R³ groupsare bonded; R⁹, R¹⁰ and R¹¹, taken separately, represent, simultaneouslyor independently, a hydrogen atom, a C₁-C₈ linear, branched or cyclicalkyl or alkenyl group optionally substituted or a C₆ to C₁₀ aromaticgroup optionally substituted; two adjacent or geminal R⁹, takentogether, may form a, preferably C₅ to C₈, ring including the carbonatom to which the R⁹ groups are bonded; a R¹⁰ group and a R⁹ group, inα-position to the same N atom, can be bonded together to form a C₄-C₆ring; two adjacent R¹¹ groups can be bonded together to form a C₆ to C₁₀aromatic ring optionally substituted or a C₅-C₁₂ metallocediyl groupoptionally substituted and including the carbon atom to which the R¹¹groups are bonded; and k are, simultaneously or independently, equal to0 or
 1. 6. The process according to claim 1, wherein L4 is a ligand offormula

wherein the dotted lines indicate a single or double bond; R² and R³,taken separately, represent simultaneously or independently a linear,branched or cyclic alkyl group containing 1 to 6 carbon atoms or aphenyl group optionally substituted; or the two R² and R³ bonded to thesame P atom, taken together, form a ring having 5 to 7 atoms andincluding the phosphorus atom to which they are bonded; R⁹, R¹⁰ and R¹¹,taken separately, represent, simultaneously or independently, a hydrogenatom, a C₁-C₄ linear or branched alkyl group optionally substituted or aphenyl group optionally substituted; the two R⁹, taken together, mayform a C₄-C₈ ring including the carbon atom to which the R⁹ groups arebonded; two adjacent R¹¹, taken together, may form a phenyl groupoptionally substituted and including the carbon atom to which the R¹¹groups are bonded; and k are, simultaneously or independently, equal to0 or
 1. 7. The process according to claim 1, wherein the base has apK_(a) above
 14. 8. The process according to claim 1, wherein the baseis an alkaline or alkaline-earth metal carbonates, an alkaline oralkaline-earth metal hydroxides, C₁₋₁₀ amidures, C₁₀₋₂₆ phosphazene oran alcoholate of formula (R¹³O)₂M or R¹³OM′, wherein M is analkaline-earth metal, M′ is an alkaline metal or an ammonium NR¹⁴ ₄ ⁺,R¹³ stands for hydrogen or a C₁ to C₆ linear or branched alkyl radicaland R¹⁴ stands for a C₁ to C₁₀ linear or branched alkyl radical.
 9. Theprocess according to claim 1, wherein the substrate is a compound offormula (I)

wherein R^(a) and R^(b) represent, simultaneously or independently, alinear, branched or cyclic C₁-C₃₀ aromatic, alkyl or alkenyl groupoptionally substituted; or R^(a) and R^(b) are bonded together and forma C₄-C₂₀ saturated or unsaturated group, optionally substituted; andwherein the substituents of R^(a) and R^(b) are a COOR^(c), group, one,two or three halogen, OR^(c), NR^(c) ₂ or R^(c) groups, in which R^(c)is a hydrogen atom, a halogenated C₁-C₂ group or a C₁ to C₁₀ cyclic,linear or branched alkyl, or alkenyl group.
 10. A ligand of formula(2′), (4-B′) or (4-C′)

wherein k are, simultaneously or independently, equal to 0 or 1; R² andR³, when taken separately, represent, simultaneously or independently, alinear, branched or cyclic C₁ to C₈ alkyl or alkenyl group optionallysubstituted, a C₆ to C₁₀ aromatic group optionally substituted, or anOR^(2′) or NR^(2′)R^(3′) group, R^(2′) and R³′ being a C₁ to C₈ alkyl oralkenyl group; or the groups R² and R³ bonded to the same P atom, whentaken together, form a saturated or unsaturated ring optionallysubstituted, having 4 to 10 atoms and including the phosphorus atom towhich the R² and R³ groups are bonded; A represents a —(CR⁹ ₂)_(k)—group or a diphenyl, dinaphthyl, C₅-C₁₂ metallocediyl, phenylene(—C₆H₄—) or naphthylene (—C₁₀H₆—) group optionally substituted; Brepresents a diphenyl, dinaphthyl, C₅-C₁₂ metallocediyl, phenylene ornaphthylene group optionally substituted or a group of formula

R⁹, R¹⁰ and R¹¹, taken separately, represent, simultaneously orindependently, a hydrogen atom, a C₁-C₁₀ linear, branched or cyclicalkyl or alkenyl group optionally substituted or a C₆ to C₁₀ aromaticgroup optionally substituted; two adjacent or geminal R⁹, takentogether, may form a C₅₋₁₀ ring including the carbon atom to which theR⁹ groups are bonded; a R¹⁰ group and a R⁹ group, in α-position to thesame N atom, can be bonded together to form a C₄-C₆ saturated orunsaturated ring; two adjacent R¹¹ groups can be bonded together to forma C₅ to C₁₀ aromatic ring optionally substituted or a C₅-C₁₂metallocenediyl group optionally substituted and including the carbonatom to which the R¹¹ or R⁹ groups are bonded; and and wherein thesubstituents of A, B, R², R³, R⁹, R¹⁰ and R¹¹ are one or two halogen, C₁to C₁₀ alkoxy, polyalkyleneglycols, halo- or perhalo-hydrocarbon, COOR,NR₂, quaternary amine or R groups, wherein R is a C₁ to C₆ alkyl, or aC₅ to C₁₂ cycloalkyl, aralkyl or aromatic group, the latter being alsooptionally substituted by one, two or three halogen, sulfonates groupsor C₁-C₈ alkyl, alkoxy, amino, nitro, sulfonates, halo- orperhalo-hydrocarbon or ester groups.
 11. A ligand of formula (4-F) or(4-G)

wherein Ph is phenyl radical, R, taken separately, is C₁-C₅ alkyl or,taken together, are a C₃-C₆ group, and k is 1 or 0; provided thatN,N′-1,2-ethanediylidenebis[2-(diphenylphosphino-)benzenemethanamine andN,N′-2,3 -butanediylidenebis[2-(diphenylphosphino-)benzenemethanamineare excluded.
 12. A complex of formula (1) or (2)[Ru(L4)Y₂]  (1)[Ru(L4)(X)_(n)(Y)_(2-n)](Z)_(n)  (2) wherein each Y represents,simultaneously or independently, CO, a hydrogen or halogen atom, ahydroxyl group, or a C₁-C₆ alkoxy or carboxylic radical, or a BH₄ orALH₄ group; X represents a C₃-C₃₀ mono-phosphine or a solvent; Zrepresents a non-coordinated anion; and n is 0, 1 or 2, and L4 is aligand of formula (2′), (4-B′), (4-C′), (4-F) or (4-G) as defined inclaim 11, provided that dichloro [N,N′-1,2-ethanediylidenebis[2-(diphenylphosphino-κP)benzenemethanamine-κM-Ruthenium is excluded.